Are OTC statins lowering the nation's cholesterol?

Statins work by inhibiting the production of cholesterol in the liver. Over 80% of cholesterol is produced in the liver by a multistep process. The specific enzyme in this pathway is hydroxyl-methoxy-gluteryl coenzyme A (HMG-CoA), and statins are HMG-CoA reductase inhibitors.Statins are extremely effective at reducing the amount of cholesterol produced by the liver and have been shown to reduce low-density lipoprotein (LDL) cholesterol by up to 60% (see Table 1). They are also responsible for an increase in the number of LDL receptors on the liver surface. This results in an upregulation in the amount of cholesterol taken back to the liver for excretion. The net result of this is a decrease in the circulating levels of cholesterol.

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Cholesterol is a fat that is necessary for the healthy functioning of the body. It is used in sex hormones, bile salts and for cell repair and functioning. However, too much cholesterol can lead to a buildup of fatty plaques that can obstruct blood flow in both arteries and veins. In some cases, plaques can rupture causing an embolus/thrombus to be thrown into the circulation, with the potential to cause damage in other parts of the body.(1)Cholesterol is not soluble in water and therefore needs some sort of mechanism to enable it to be carried around the body. Protein-bound buckets known as lipoproteins are used to transport the cholesterol from the liver, where it is made, around the body, where it is used, and back to the liver for excretion. Low-density lipoproteins (LDL cholesterol, or "bad" cholesterol) carry the cholesterol from the liver, while high-density lipoproteins (HDL cholesterol, or "good" cholesterol) carry it back for excretion. Statins reduce LDL cholesterol and have a minor impact in reducing triglycerides (TGs), while slightly increasing HDL cholesterol.Reducing cholesterol reduces cardiovascular risk.(2) Statin therapy reduces cholesterol when prescribed effectively.(3) There are over 25 years' worth of safety data on statin therapy.(4,5) They are a tried and tested medication, and there is a wealth of data available for their safe and effective use.(6-11) In fact, some physicians will suggest that statin therapy is safer than aspirin - a common resident in many a household medicine ­cabinet.There are a limited number of side-effects that people who are on statins complain of. These include:

A transient gastrointestinal effect, which has been demonstrated with all lipid-lowering medication to date.

Abnormal liver function tests, although the ­significance of these is unknown as many people will have altered liver function test results on no medication that resolve spontaneously.

Muscle aches and pains. These are relatively ­common; however, a general flu-like feeling may indicate rhabdomyolysis (an acute, sometimes fatal, disease marked by destruction of skeletal muscle), which while rare (occurs in 1 in 106 patients) is significant and warrants further ­investigation. A number of risk factors for ­rhabdomyolysis have been identified - older age, lower body weight, hypothyroidism, concomitant therapy and other drugs (mostly metabolised through pathway CP450 3A4: eg, "conazole" ­antifungals, gemfibrozil, ciclosporin and HIV ­protease inhibitors).

Statins are contraindicated in people with active liver disease and those with excessive alcohol intake. They should not be taken by pregnant women or women trying to conceive, nor should they be used while breastfeeding. Their use in children and adolescents is the subject of much investigation.(12,13)Slight changes in the molecular structure of the drug make each statin slightly different.

Over-the-counter statinsAn initiative in July 2004 from the Medicines and Health Regulatory Authority made 10mg of simvastatin directly available from their pharmacist to persons deemed to be at moderate risk of developing coronary heart disease (CHD).Those wanting to take advantage of the new over-the-counter (OTC) statins will first have to answer a series of screening questions to determine their suitability for the drug. These questions are aimed at screening out those most at risk (eg, those with diabetes or a previous history of heart disease or genetic dyslipidaemias). Those who are at high risk of CHD will be referred to their GP for further advice and information.All people requesting OTC statins will be exposed to lifestyle advice and information directly from their pharmacist.Contraindications for the drug include a family history of known thyroid disease (this may make rhabdomyolysis more likely if the thyroid disease is undetected). Some drugs are also contraindicated - the antiviral "onazole" group is specifically implicated as it may interact with the statin.Those who are at moderate risk of CHD (10% risk over the next 10 years) include males and females over 55 years of age, and males aged between 45 and 54 years of age who have one other risk factor for heart disease - smoking, overweight, family history of heart disease (65 years in female relatives, and 55 years in male relatives) or of South Asian origin.When the drug is dispensed the pharmacist will encourage that person to inform their GP.There is no requirement to have a cholesterol test before starting the statin drug. However, the person should be encouraged to have a cholesterol test as this will show the level of cholesterol before they start on the statin, and the level after six months of 10mg statin treatment. Annual checkups of cholesterol level will monitor progress and will highlight any significant changes. If the person's cardiac risk factor profile changes, the pharmacist is on hand to advise them what to do specifically and to refer them to primary care colleagues as appropriate.The initiative was launched in July 2004. It was met by a range of reactions from various groups and individuals. Some professional groups were not keen on the idea, stating that 10mg was a suboptimal dose and that a higher dose would have more benefit for those at risk of developing heart disease. However, 10mg of a statin can lead to a 27% reduction in LDL cholesterol,(14) which in turn gives a significant reduction (25-30%) in the risk of myocardial infarction, coronary artery bypass graft, percutaneous coronary angioplasty and stroke. The fact that doubling the dosage of a statin drug on the whole will give an extra 6% reduction in LDL cholesterol should not be overlooked, but the majority of people will receive a significant and adequate reduction with the 10mg tablet.Another argument against the initiative is that, by making those at moderate risk of heart disease pay for the medication, we are creating a two-tiered system whereby some people are able to afford the medication while others are not. However, this really is a question of leaving the choice up to the individual. Some people choose to spend their money on cigarettes, excessive amounts of alcohol or fast food. That is their choice. The medication works out as cheaply as some of the cholesterol-lowering plant-sterol or plant-stanol products that are currently on the market. It is up to the individual to decide whether they wish to take the medication or not. However, the pharmacist should stress that this medication is for life and that it is therefore not a decision to be made quickly or in an uninformed manner.People generally want to know what their CHD risk is and are keen to receive information in a consumer-friendly and professional way, supplied by the pharmacist. It is good to note that OTC simvastatin is not being offered as a panacea to heart healthcare, but, instead, the information is being offered to consumers and is targeted to their level of risk.However, the burden of improving the health of our nation, something which nurses and doctors have tried for a long time to improve, is now being shared with our fellow health professionals - pharmacists.

The Long Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349-57.